4-Bromo-2-fluoroaniline → 4-((4-Bromo-2-fluorophenyl)amino)-7-methoxyquinazolin-6-yl acetate

HRID 1351214Notes

Reaction equation

[C:1]([O:4][C:5]1[CH:6]=[C:7]2[C:12](=[CH:13][C:14]=1[O:15][CH3:16])[N:11]=[CH:10][NH:9][C:8]2=O)(=[O:3])[CH3:2].[Br:18][C:19]1[CH:25]=[CH:24][C:22]([NH2:23])=[C:21]([F:26])[CH:20]=1>O=S(Cl)Cl.CN(C=O)C>[C:1]([O:4][C:5]1[CH:6]=[C:7]2[C:12](=[CH:13][C:14]=1[O:15][CH3:16])[N:11]=[CH:10][N:9]=[C:8]2[NH:23][C:22]1[CH:24]=[CH:25][C:19]([Br:18])=[CH:20][C:21]=1[F:26])(=[O:3])[CH3:2]

Participants

Conditions

Temperature: 100 °C

Procedure

To a solution of 6-acetoxy-7-methoxy-quinazolin-4-one (RO0505111-000) (1.0 g, 4.26 mmol) (from Example 15, Step A, supra) in SOCl2 (12.5 mL) (Aldrich) were added a few drops of DMF (0.1 mL). The reaction mixture was then heated with stirring at 100° C. for 3 hours. The solvents were evaporated and the residue was dried in vacuo. The residue was dissolved in 2-propanol (20 mL), then 4-bromo-2-fluoroaniline (0.891 g, 4.69 mmol) (Aldrich) was added. The reaction mixture was heated at 110° C. for 3 hours. The reaction mixture was cooled to room temperature and filtered. The precipitate was collected and dried in vacuo to give 6-acetoxy-4-(4-bromo-2-fluoro-phenylamino)-7-methoxy-quinazoline as a gray solid. (Yield 1.42 g, 82%).

Workup

temperatureThe reaction mixture was then heated
customThe solvents were evaporated
customthe residue was dried in vacuo
dissolutionThe residue was dissolved in 2-propanol (20 mL)
temperatureThe reaction mixture was heated at 110° C. for 3 hours
temperatureThe reaction mixture was cooled to room temperature
filtrationfiltered
customThe precipitate was collected
customdried in vacuo

Sources & evidence

ORD record: ord-0764fab8a5b148b39f3bdd11b85b9699
Source dataset: uspto-grants-2007_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07217717B2

Reaction notes

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